Risperidone Combination Therapy With Propentofylline for Treatment of Irritability in Autism Spectrum Disorders: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Objectives Propentofylline is a xanthine phosphodiesterase inhibitor and adenosine reuptake blocker with neuroprotective effects linked to anti-inflammatory and antiexcitatory properties. This is a double-blind, placebo-controlled trial investigating the potential beneficial effects of propentofylline, as an adjunctive treatment with risperidone, on the severity and behavioral abnormalities of autism spectrum disorder (ASD). Methods A total of 48 children with ASD were randomly allocated into 2 groups of risperidone (initiating at 0.5 mg/d) plus propentofylline (initiating at 300 mg/d) and risperidone plus placebo. The Aberrant Behavior Checklist—Community (ABC-C) and Childhood Autism Rating Scale (CARS) were used for the evaluation of ASD severity and behavioral disruptions at baseline, week 4, and week 10. Primary outcome measure of the study was ABC-C irritability subscale score, whereas CARS score along with other 4 subscales of ABC-C (lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech subscales) were considered as secondary outcome measures. Results Results from the general linear model repeated measures analysis demonstrated significant time-treatment interaction on irritability subscale ( F 1.55 = 3.45; P = 0.048) and CARS ( F 1.41 = 4.08; P = 0.034) scores. Compared with the placebo group, children receiving propentofylline showed greater improvements in the CARS score ( P = 0.037) from baseline to the study endpoint. Our results found no significant time-treatment effect on other subscales of ABC-C. Two trial groups were comparable based on the frequency of adverse effects. Conclusions Our findings demonstrated that adjunctive treatment with propentofylline is effective in alleviating disease severity and improving irritability in ASD patients. However, larger studies with longer durations are required to confirm these results.